Riboflavin derivatives and process for their preparation



Patented Sept. 19

amomvnv nnmvs'rivns is raocass ron mm rasrsasrrou r Gustav A. Stein,Plainfleld, and William 1.1mm,

J Inc.,

- No Drawing.

Serial No.455,546

Grantord, N. 1., assignors to Merck a 00., f

Rahway,-N. 1., a corporation of New Jersey Application August 20, 1942',

1'! Claims. (Cl; 260-211) This invention relates to novel organicchemical compounds and to methods of preparing the same. Specifically,it is concerned with derivatives of the growth-promoting factorriboflavin and to processes for synthesizing said derivatives.

The riboflavin derivatives according to the present invention areobtained by reacting riboflavin or an alkali metal salt oi riboflavinsuch as sodium riboflavin, with a polybasic organic carboxylic acid suchas phthalic acid, succinic acidand anhydrides of said acids. Thesecompounds, particularly the succinate have solubility properties whichfacilitate their administration andalso possess the advantage over othermaterials, such as sodium riboflavin, that they form aqueous solutionshaving about the same hydrogen ion concentration (pH about 8)v as ispresent in the human blood stream, thus making them suitable forinjection administration.

The following examplesillustrate methods of carrying out the presentinvention, but it is to be understood that these examples are given byway oi illustration and not 01! limitation.

Example 1 About .001 mol. of sodium riboflavin is refluxed .forapproximately 14 hours in about 250 cc. of anhydrous pyridine with about.002 mol. of succinic anhydride. After'evaporation of the pyridine, theresidue is dissolved in water and acidifled with 10% phosphoric acid.The crystals which separate are removed and recrystallized twice fromboiling water. The orange-red amorphous substance so obtained decomposesat 218- 220 C.

Example 2 About .001 mol. of riboflavin is refluxed for approximately 14hours in about 250 cc. oi-anhydrous pyridine with .002 mol. of succinicanhydride. Aiter evaporation of the pyridine the:

residue is acidified with 10% phosphoric acid and the amorphousinsoluble material is removed and twice recrystallized irom boilingwater. Aiter drying the deep orange residue decomposes at 218-219uncorrected. v

Modifications may be made in carrying out the present invention withoutdeparting irom the spirit and scope thereof and theinvention is to belimited only by the appended claims.

What is claimed is: i

l. A condensation p uct of a substance selected from the classconsisting of riboflavin and alkali metal salts oi riboflavin with asubstance selected .110111 the group consisting oi phthalicacid'anhydride and succinic. acid anhydride.

2. A condensation product of a substance selected from the classconsistin of riboflavin and. alkali metal salts of riboflavin withsuccinic acid anhydride.

in pyridine 3. -A condensation product oi sodium riboflavin and succinicacid anhydride.

4. The process that comprises condensing a substance selected from theclass consisting of riboflavin and alkali metal salts of riboflavin witha substance selected from the class consisting oi phthalic anhydride andsuccinic anhydride.

5. The process. that com se condensing a substance selected from theclass consisting oi."

riboflavin and alkali metal salts of riboflavin with succinic anhydride.

6. The process that comprises condensing riboflavin with succinic acidanhydride.

'1. The process that comprises condensing sodium riboflavin withsuccinic acid anhydride.- 8. The process that comprises condensing asubstance selected from the class consisting oi riboflavin and alkalimetal salts of riboflavin with a substance selected from the classconsisting of Y phthalic anhydride and succinic anhydride in thepresence of a substantially inert-solvent.

9. The process that comprises condensing a substance selected from theclass consistlns oi, riboflavin and'alkali metal salts of riboflavinwith.

succinic anhydride in the presence of a'substantially inert solvent. 10.The :process presence oi a substantially inert solvent.

v 11. The process that comprises condensing sodlum riboflavin withsuccinic acid anhydride in I the presence of a 12. The processsubstantially inert solvent."

flavin and alkali metal' salts of riboflavin with'a substance selectedfrom the V phthalic anhydride and succinic anhydride in the presence ora substantially inert solvent at an elevated temperature.

13. The process that comprises reacting a substance selected from theclass consisting oiriboflavin and alkali metal salts of riboflavin withsuccinic anhydride in the presence of a substantially inert solvent atan elevated temperature.

14. The process that comprises reacting ribO-'-' flavin with succinicacid anhydride in the pr'esv ence of a substantially inert solvent at anelevated temperature.

15. The process that comprises reacting riboflavin with succinic acidanhydride in the presence oi a substantially inert solvent at anelevated temperature.

16. The process that comprises refluxing amixture or riboflavin andsuccinic anhydride in pyri-' dine.- 1'1. The process that comprisesrefluxing a mixture of sodium riboflavin-and succinic anhydride (many a.WIILIAH .1. MORAN. on.

' that {comprises condensing riboflavin with succinic acid anhydried inthe that comprises reacting a-substance selected from the classconsisting of iibo-.

class consisting oi 1 sodium'

